P399: SUCCESSFUL IMPLEMENTATION OF A MODIFIED ST JUDE TOTAL XV PROTOCOL FOR TREATING CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA IN LEBANON. LESSONS FOR LOW- AND MIDDLE-INCOME COUNTRIES.
Authors: Lara Ghaddar, Raphah Burghol, Samar Muwakkit
Journal: HemaSphere (2023)

Background: Over a previous era (1), we had implemented the St. Jude Total XV protocol for treating childhood acute lymphoblastic leukemia at the Children’s Cancer Center of Lebanon and seen remarkable improvements in survival rates. However, patients experienced serious bacterial, viral, and fungal infections requiring intensive care admission, infection-related mortality, CNS toxicities, CMV retinitis, and a reduced quality of life during remission. To address these issues, starting January 2016 we amended the St Jude Total XV protocol by stopping vincristine and dexamethasone pulses at week 69 of maintenance and decreasing VCR dose to 1.5mg/m2 (max 2mg). (1) Muwakkit S, Al-Aridi C, Samra A, Saab R, Mahfouz RA, Farra C, Jeha S, Abboud MR. Implementation of an intensive risk-stratified treatment protocol for children and adolescents with acute lymphoblastic leukemia in Lebanon. Am J Hematol. 2012 Jul;87(7):678-83. doi: 10.1002/ajh.23222. Epub 2012 May 6. PMID: 22565284. Aims: To improve survival rates and decrease severe infections, CMV retinitis and death during remission. Methods: A retrospective chart review was conducted of 127 consecutive patients aged 1-18 years who were treated for acute lymphoblastic leukemia at the Children’s Cancer Center of Lebanon (CCCL– AUBMC) from January 2016 to January 2022. Treatment was per modified St. Jude Total XV protocol with omission of vincristine and dexamethasone pulses after week 69 maintenance. Overall survival and event free survival were estimated using the Kaplan-Meier estimate methods. Results: Risk stratification was as follows: intermediate-/high-risk 71 patients (55.9%) and low-risk 56 patients (44%). Using the NCI risk criteria, 62 patients (48.8%) were standard-risk and 65 (51.1%) were high-risk. No patients died during remission induction secondary to sepsis. No patients developed CMV retinitis, disseminated varicella nor orbital cellulitis.One patient required admission to the intensive care unit due to severe pneumonia.One patient developed posterior reversible encephalopathy syndrome.None developed progressive multifocal leukoencephalopathy. Reactivation of CMV and EBV after week 120 occurred in 10 males as males were treated for 146 maintenance weeks. None died. Discontinuing chemotherapy completely reversed this reactivation in all but two patients who received rituximab and/or antiviral therapy alongside discontinuation of treatment. Two developed EBV lymphoproliferative disease while one patient had secondary hemophagocytic lymphohistiocytosis. All recovered eventually. 14 out of 127 patients relapsed with 11 males and 3 females having a median age 8 years at relapse time (mean 9.7yrs; range 3-17yrs). Four were on LR arm while 10 were on Int/High Risk arm. Seven out of 14 died. Two died after developing secondary AML. Kaplan Meir estimates of two eras in table 3.Summary/Conclusion The results of this study suggest that omitting vincristine plus dexamethasone pulses after week 69 of maintenance for patients with low- and intermediate risk acute lymphoblastic leukemia in children can be done safely without leading to an inferior outcome. This could potentially reduce the burden on healthcare systems, improve quality of life for those affected by childhood acute lymphoblastic leukemia, and reduce costs associated with long term maintenance therapy. Furthermore, it was associated with elimination of CMV retinitis and death during remission as well as less severity of viral illnesses. We anticipate that by stopping maintenance chemotherapy at 120 weeks for all males we can significantly reduce the incidence of late CMV and EBV reactivation. Keywords: Acute lymphoblastic leukemia, Chemotherapy toxicity, EBV, Relapse